INDEFINITE SURVIVAL OF NEURAL XENOGRAFTS INDUCED WITH ANTI-CD4 MONOCLONAL-ANTIBODIES

Xenografts of neural tissue are usually rapidly rejected when transpla nted into the central nervous system of adult recipient animals. This study has examined the cell mediated immune response to both concordan t (between closely related species) and discordant (between distantly related species) neural xenografts in the mouse, and has investigated the role of the CD4(+) and CD8(+) T lymphocyte subsets in this process using monoclonal antibodies specific for the CD4 and CD8 cell surface glycoproteins. We have established that: (1) in this model system con cordant neural xenograft rejection occurs within 15-30 days; however, xenograft survival can be dramatically prolonged with CD4(+), but not CD8(+), T lymphocyte depletion; (2) the administration of two successi ve courses of a high dose of anti-CD4 monoclonal antibody treatment re sults in indefinite concordant neural xenograft survival; (3) the mech anism by which the high dose anti-CD4 monoclonal antibody therapy appe ars to function involves the depletion of intrathymic CD4(+) cells; (4 ) anti-CD4 monoclonal antibody treatment enhances discordant neural xe nograft survival, to beyond 60 days in many cases.These results demons trate that CD4(+) T lymphocytes are of central importance in the immun e response to both concordant and discordant neural xenoantigens. Thus the use of anti-CD4 monoclonal antibody therapy is an effective strat egy to prolong significantly the survival of xenogeneic neural transpl ants. Furthermore this treatment caused no obvious deleterious side-ef fects. These findings have implications for future cross-species studi es in experimental neurobiology and, possibly, in clinical neural tran splantation.